Prostaglandin derivatives, particularly travoprost, bimatoprost and latanoprost of the following formula (2) have been extensively used due to their clinical effects such as reducing intraocular pressure and promoting hair and eyelash growth.

The prostaglandin derivatives have been conventionally prepared through many synthetic steps in poor yields. The most common commercial processes use Corey lactone as a starting material to produce the prostaglandin derivatives, as shown in the following Reaction Scheme 1 (see E. J. Corey et al., J. Amer. Chem. Soc., 91, 5675-5677, 1969). However, Corey lactone is expensive and the processes require a chromatographic separation for removing β-OH which is produced as a by-product on the reduction of 15-ketone group into α-OH after the introduction of ω-chain. Therefore, the processes are unsuitable for large-scale production of the prostaglandin derivatives in terms of poor yields and high costs. The β-OH produced as a by-product may be reduced by using a chiral borane compound as a stereoselective reducing agent, but the chiral borane compound is also very expensive.

To overcome the above disadvantages, it was suggested to prepare the prostaglandin derivatives by conjugate addition of ω-chain including α-OH to cyclopentenone derivatives having α-side chain, as shown in the following Reaction Scheme 2. In particular, a process developed by Lipshuts et al. can stereoselectively introduce ω-chain by using higher order mixed organocuprate (see U.S. Pat. Nos. 4,785,124, 4,904,820, 4,952,710 and 5,055,604, and WO 02/090324).

Such process requires that, in order to synthesize prostaglandin F (PGF) derivatives, the ketone group on the cyclopentanone ring of the prostaglandin E (PGE) derivatives obtained from the conjugate addition should be stereoselectively reduced to α-OH. The use of sodium borohydride (NaBH4) as a reducing agent gives the PGF derivatives in the form of a 6:4 mixture of α-OH and β-OH, and the use of a bulky hydride such as L-selectride, N-selectride, K-selectride and LS-selectride gives the PGF derivatives in increased selectivity of 9:1 (α:β ratio). However, a significant amount of β OH should be still removed by using a difficult method causing large yield loss.
Therefore, there has been a need to develop a process for more stereoselectively reducing the ketone group on the cyclopentanone ring of the prostaglandin E derivatives.